Human Ccr4 and Caf1 Deadenylases Regulate Proliferation and Tumorigenicity of Human Gastric Cancer Cells via Modulating Cell Cycle Progression

Cancers

Li-Na Zhang¹  Yong-Bin Yan²  Xu-Ying Zheng²  Jia-Qian Liu²  Xiao-Hui Song²  Zhe-Wei Zhang²  Xiao-Yan Liao² 

[1] College of Life Science and Chemistry, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China;State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;

关键词: Caf1;    Ccr4;    Ccr4-Not complex;    cell cycle progression;    deadenylase;    mRNA decay;   

DOI  :  10.3390/cancers13040834

来源: DOAJ

【 摘 要 】

Cancer cells generally have reprogrammed gene expression profiles to meet the requirements of survival, continuous division, and metastasis. An interesting question is whether the cancer cells will be affected by interfering their global RNA metabolism. In this research, we found that human Ccr4a/b (hCcr4a/b) and Caf1a/b (hCaf1a/b) deadenylases, the catalytic components of the Ccr4-Not complex, were dysregulated in several types of cancers including stomach adenocarcinoma. The impacts of the four deadenylases on cancer cell growth were studied by the establishment of four stable MKN28 cell lines with the knockdown of hCcr4a/b or hCaf1a/b or transient knockdown in several cell lines. Depletion of hCcr4a/b or hCaf1a/b significantly inhibited cell proliferation and tumorigenicity. Mechanistic studies indicated that the cells were arrested at the G2/M phase by knocking down hCaf1a, while arrested at the G0/G1 phase by depleting hCaf1b or hCcr4a/b. The four enzymes did not affect the levels of CDKs and cyclins but modulated the levels of CDK–cyclin inhibitors. We identified that hCcr4a/b, but not hCaf1a/b, targeted the p21 mRNA in the MKN28 cells. Furthermore, depletion of any one of the four deadenylases dramatically impaired processing-body formation in the MKN28 and HEK-293T cells. Our results highlight that perturbating global RNA metabolism may severely affect cancer cell proliferation, which provides a potential novel strategy for cancer treatment.

【 授权许可】

Unknown